Diverse initial stimuli may contribute to the pathogenesis of Rheumatoid Arthritis (RA). However, B cell activation and autoantibody production constitutes essential steps in the progression of RA. To address possible mechanisms leading to the induction of autoantibodies in RA, we propose to analyze disease progression in a new model for systemic autoimmunity. This model was derived by constructing homozygous deletion mutants in three structurally related tyrosine kinase receptors, Mer, Ax1, and Tyro3. The following experiments are proposed: 1. Isolate hybridomas from Mer, Ax1, and Tyro3 triple deletion homozygous mice. 2. Characterize the binding and immunoglobulin V gene sequences of autoantibodies directed against collagen type II, glucose-6-phosphate isomerase (GPI), and apoptotic cells. 3. Explore the pathogenic potential of selected autoantibodies by transferred purified monoclonal IgG autoantibodies into naive animals. The analysis of the proposed experiments will guide subsequent steps toward securing extramural funding for studies of antibody-mediated joint erosion.